Conductance mutations of the nicotinic acetylcholine receptor do not act by a simple electrostatic mechanism

P. Kienker, Gordon F. Tomaselli, M. Jurman, G. Yellen

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Fixed negative charges in many cation channels raise the single-channel conductance, apparently by an electrostatic mechanism: their effects are accentuated in solutions of low ionic strength and attenuated at high ionic strength. The charges of specific amino acids near the ends of the proposed pore-lining M2 segment of the nicotinic acetylcholine receptor, termed the extracellular and cytoplasmic rings, have recently been shown to influence the single-channel K+ conductance (Imoto, K., C. Busch, B. Sakmann, M. Mishina, T. Konno, J. Nakai, H. Bujo, Y. Mori, K. Fukuda and S. Numa. 1988. Nature 335:645–648). We examined whether these charges might act by a direct electrostatic effect on the energy of ions in the pore, rather than indirectly by inducing a structural change. To this end, we measured the conductances of charge mutants over a range of K+ concentrations (ionic strengths). As expected, we found that negative charge mutations raise the conductance, and positive charge mutations lower it. The effects of cytoplasmic-ring mutations are accentuated at low ionic strength, but they are not completely attenuated at high ionic strength. The effects of extracellular-ring mutations are independent of ionic strength. These results are inconsistent with the simplest electrostatic model. We suggest a modified model that qualitatively accounts for the data.

Original languageEnglish (US)
Pages (from-to)325-334
Number of pages10
JournalBiophysical Journal
Volume66
Issue number2
DOIs
StatePublished - Jan 1 1994
Externally publishedYes

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Nicotinic Receptors
Static Electricity
Osmolar Concentration
Mutation
Cations
Ions
Amino Acids

ASJC Scopus subject areas

  • Biophysics

Cite this

Conductance mutations of the nicotinic acetylcholine receptor do not act by a simple electrostatic mechanism. / Kienker, P.; Tomaselli, Gordon F.; Jurman, M.; Yellen, G.

In: Biophysical Journal, Vol. 66, No. 2, 01.01.1994, p. 325-334.

Research output: Contribution to journalArticle

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